Many physiologically active substances such as pharmaceuticals, agricultural chemicals, perfumes, and sweeteners comprise a partial structure of alcohol having an asymmetric carbon atom. Optical isomers can be present in such a compound. However, there may be a significant difference in the degree of physiological activity among these optical isomers. Some isomers exhibit physiological activity quite different from others. Therefore, development of a method for separating an optical isomer mixture of an alcohol or a compound having a partial structure of alcohol (hereinafter both simply referred to as “alcohol”) easily and surely has been desired.
However, the mixture can rarely be separated into two optical isomers without being influenced by an external optically active factor. Spontaneous resolution or the like rarely occurs. There are no general rules for separating the mixture. Accordingly, in almost all cases, it is highly difficult to assess whether or not an optical isomer mixture of an alcohol can be separated into optically active compounds. The mixture is not easily separated in almost all cases.
As an example of optically resolving an alcohol, Synlett., (6), 862 (2000), J. Org. Chem., 64, 2638 (1999), and the like describe a method comprising allowing one of optical isomers to remain as the alcohol and transforming the other optical isomer into an ester derivative in a natural optically active environment (for example, internal organs of animals containing an esterified enzyme or hydrolyzed enzyme). However, since such an enzyme does not have chemical stability, in particular, thermal stability, the enzyme cannot be used under high temperature conditions. Further, it is difficult for the enzyme to be generally and widely accepted due to its high cost and difficulty in procuring in a large amount.
Tetrahedron Lett., 35, 4397 (1994) reported an experiment in which an ester prepared by condensing a carboxylic acid having an asymmetric carbon atom with an alcohol was separated into individual diastereomers by silica gel column chromatography. In principle, this is optical resolution of an alcohol. However, since there are no general rules or principles for producing a highly separable diastereomer mixture, the method cannot be generally applied.
The present invention has been achieved in view of such a situation. Accordingly, the present invention provides a novel optical resolving reagent that can optically resolve an optical isomer mixture of an alcohol, having an asymmetric carbon atom in the molecule, easily and industrially advantageously, and a method for optically resolving an alcohol using the optical resolving reagent.